CD271 Expression on Patient Melanoma Cells Is Unstable and Unlinked to Tumorigenicity

Boyle, Samantha E.; Fedele, Clare G.; Corbin, Vincent; Wybacz, Elisha; Szeto, Pacman; Lewin, Jeremy; Young, Richard J.; Wong, Annie; Fuller, Robert; Spillane, John; Speakman, David; Donahoe, Simon; Pohl, Miklos; Gyorki, David E.; Henderson, Michael A.; Johnstone, Ricky W.; Papenfuss, Anthony T.; Shackleton, Mark

doi:10.1158/0008-5472.can-15-2377

Cited by 26 publications

(33 citation statements)

References 46 publications

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“…Previous studies indicate that CD271 expression within primary melanomas correlates with a more aggressive tumour phenotype and reduced patient survival, while isolated CD271‐expressing cells from primary melanomas initiate tumour growth in immunocompromised NRG mice at a higher rate than CD271 – cells . Conversely, other studies suggest that, rather than being a marker of distinctive melanoma‐initiating subpopulations, CD271 expression is induced during acquired resistance to BRAF inhibition, DNA‐damaging drugs or ethanol . Collectively, these studies indicate that CD271 is a biomarker of tumour progression and is consistent with the concept that CD271 signalling constitutes a stress‐tolerance mechanism within tumour cells.…”

supporting

confidence: 77%

Harnessing autophagy to overcome mitogen‐activated protein kinase kinase inhibitor‐induced resistance in metastatic melanoma

et al. 2018

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supporting

confidence: 77%

Harnessing autophagy to overcome mitogen‐activated protein kinase kinase inhibitor‐induced resistance in metastatic melanoma

et al. 2018

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“…CD271 expression - like other melanoma markers - underlies phenotype switching responsible for fluctuations of CD271 expression 44 , 50 . We demonstrated that A375 cells with stable over expression of CD271 are indeed capable of migration in brain slices.…”

Section: Discussionmentioning

confidence: 99%

CD271 determines migratory properties of melanoma cells

Radke

Roßner

Redmer

2017

Sci Rep

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Melanoma cell expression of the nerve growth factor receptor CD271 is associated with stem-like properties. However, the contributing role of the receptor in melanoma cell migration is elusive. Here, we explored extracranial (skin, soft tissue, lymph node and liver, n = 13) and matched brain metastases (BM, n = 12) and observed a heterogeneous distribution of phenotypically distinct subsets of CD271+ cells. In addition, we observed that CD271 expression gradually rises along with melanoma progression and metastasis by exploration of publicly available expression data of nevi, primary melanoma (n = 31) and melanoma metastases (n = 54). Furthermore, we observed highest levels of CD271 in BM. Sub-clustering identified 99 genes differentially expressed among CD271high and CD271low (p < 0.05) BM-subgroups. Comparative analysis of subsets revealed increased ( ≥ 1.5fold, log2) expression of migration-associated genes and enrichment of CD271-responsible genes involved in DNA-repair and stemness. Live cell-imaging based scratch-wound assays of melanoma cells with stable knock-down of CD271 revealed a significantly reduced cell migration (3.9fold, p = 1.2E-04) and a reduced expression of FGF13, CSPG4, HMGA2 and AKT3 major candidate regulatory genes of melanoma cell migration. In summary, we provide new insights in melanoma cell migration and suggest that CD271 serves as a candidate regulator, sufficient to determine cellular properties of melanoma brain metastatic cells.

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“…The assay identifies all classes of genetic alterations, including base substitutions, insertions, and deletions. 19 …”

Section: Methodsmentioning

confidence: 99%

Rucaparib Monotherapy in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation

Shroff

Hendifar

McWilliams

et al. 2018

JCO Precision Oncology

158

127

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Purpose Pancreatic cancer has a poor prognosis and limited treatment options. Approximately 9% of pancreatic cancers harbor a germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation. Because poly (ADP-ribose) polymerase inhibitors have significant activity in BRCA1/2-mutant ovarian and breast cancers, RUCAPANC investigated the efficacy and safety of rucaparib in BRCA1/2-mutant pancreatic cancer. Patients and Methods RUCAPANC enrolled patients with measurable locally advanced/metastatic pancreatic cancer who had received one to two prior chemotherapy regimens. Patients received oral rucaparib (600 mg twice daily) until disease progression. The primary end point was objective response rate. Results Nineteen patients were enrolled. Sixteen of 19 BRCA1/2 mutations were germ-line; three were somatic. Patients had received a median of two prior chemotherapy regimens. Four patients achieved a response; two partial responses and one complete response (CR) were confirmed (objective response rate, 15.8%; 3 of 19), with an additional CR unconfirmed. The disease control rate (CR, partial response, or stable disease for ≥ 12 weeks) was 31.6% (6 of 19) in all patients and 44.4% (4 of 9) in those who had received one prior chemotherapy regimen. As prespecified in the protocol, enrollment was stopped because of an insufficient response rate among the first 15 patients. Treatment-emergent adverse events included nausea (63.2%) and anemia (47.4%). Grade ≥ 3 adverse events included anemia (31.6%), fatigue (15.8%), and ascites (15.8%). Secondary resistance mutations were detected in circulating free tumor DNA in two patients with a germline BRCA2 mutation. These mutations are predicted to lead to the reversion of a somatic—not germline—mutation. Conclusion Rucaparib provided clinical benefit to patients with advanced pancreatic cancer and a BRCA1/2 mutation, and demonstrated an acceptable safety profile. Additional trials of rucaparib in this population are warranted.

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CD271 Expression on Patient Melanoma Cells Is Unstable and Unlinked to Tumorigenicity

Cited by 26 publications

References 46 publications

Harnessing autophagy to overcome mitogen‐activated protein kinase kinase inhibitor‐induced resistance in metastatic melanoma

Harnessing autophagy to overcome mitogen‐activated protein kinase kinase inhibitor‐induced resistance in metastatic melanoma

CD271 determines migratory properties of melanoma cells

Rucaparib Monotherapy in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation

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